title: Degeneration of a CRISPR/Cas system and its regulatory target during the evolution of a pathogen.
abstract: CRISPR/Cas systems are bacterial RNA-guided endonuclease machineries that target foreign nucleic acids. Recently, we demonstrated that the Cas protein Cas9 controls gene expression and virulence in Francisella novicida by altering the stability of the mRNA for an immunostimulatory bacterial lipoprotein (BLP). Genomic analyses, however, revealed that Francisella species with increased virulence harbor degenerated CRISPR/Cas systems. We hypothesize that CRISPR/Cas degeneration removed a barrier against genome alterations, which resulted in enhanced virulence. Importantly, the BLP locus was also lost; likely a necessary adaptation in the absence of Cas9-mediated repression. CRISPR/Cas systems likely play regulatory roles in numerous bacteria, and these data suggest additional genomic changes may be required to maintain fitness after CRISPR/Cas loss in such bacteria, having important evolutionary implications.
authors.affiliation: Department of Microbiology and Immunology, Microbiology and Molecular Genetics Program; Emory University School of Medicine; Atlanta, GA USA; Emory Vaccine Center; Emory University School of Medicine; Atlanta, GA USA; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Sampson
authors.affiliation: Emory Vaccine Center; Emory University School of Medicine; Atlanta, GA USA; Yerkes National Primate Research Center; Emory University; Atlanta, GA USA; Division of Infectious Diseases; Department of Medicine; Emory University School of Medicine, Atlanta, GA USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Weiss
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics; D001483:Base Sequence; D005075:Biological Evolution; D064113:CRISPR-Cas Systems; D005603:Francisella / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D005604:Francisella tularensis / Q000235:genetics* / Q000472:pathogenicity*; D022761:Gene Transfer, Horizontal; D008074:Lipoproteins / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D014774:Virulence
chemical_list: D001426:Bacterial Proteins; D008074:Lipoproteins
keywords: CRISPR/Cas; bacterial evolution; bacterial pathogenesis; gene expression; regulatory RNA